The authors discuss how the sibship design can be used to detect and control for familial confounding. Family-level confounding is especially problematic when estimating modest individual-level effects in the presence of familial confounders with large effects. This circumstance arises frequently in studies which relate indicators of fetal growth, such as birth weight, to outcomes that are strongly associated with parental socioeconomic status and genes. The study by Eriksen et al. in this issue of the Journal (Am J Epidemiol. 2010;172(5):530-536) uses the sibship design to capture the relation between birth weight, gestational age, and intelligence score among Norwegian males born as singletons at 37-41 completed weeks' gestation during 1967-1984. Their study illustrates how valuable the design can be in this kind of scenario. It also illustrates the potential complexity of sibship studies and the challenges they present for appropriate interpretation.